The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

The sedimentary characteristics of the special interlayer contained in the section of the Sparking Lake dam revealed by the 8.8 Jiuzhaigou earthquake in 2017 are obviously different from the tufa in the dam body, and they are considered to be prehistoric flood relics. Based on the study of the particulate matter from the 8.8 Jiuzhaigou earthquake, this paper combines comparative petrographic, mineralogical, geochemical and chronological studies of the special interbedded sediments of the Sparking Lake dam with other genetic samples to obtain homology information and genetic links, as well as to explore the tufa depositional dynamics and earthquake disaster subsidence. The palaeoseismic benefit in the discontinuity layer is explored, and the palaeoseismic information embedded in the profiles is extracted, providing a new idea to reconstruct the palaeoseismic events in the tufa deposition sequence. According to X-ray diffraction, laser particle size analysis and scanning electron microscope experiments, the particulate matter in the Jiuzhaigou mountains has its own specific mineralogical characteristics. The mineral composition of the particulate matter is basically calcite. The particle size is large, and the single particle is mostly angular and subangular. The fracture morphology observed under the single particle microscope is uneven, showing the characteristics of dust caused by earthquake disasters. Geochemical analysis data show that the provenance of various types of particles in the same area is stable, indicating the homology of terrestrial carbonate sedimentation in the karst system. Combined with mineralogy and grain size morphology, the interbedded particles in the tufa depositional profile have the potential application of palaeoseismic archives to record extreme seismic events. The palaeoseismic date was inferred from the chronological data of special interlayered sediments in the tufa dam body. Therefore, the tufa bedding can be related to the palaeoearthquake, and the special interlayer of the tufa section can be used to reconstruct palaeoearthquakes.

Wearable thermoelectric generators (w-TEGs) convert thermal energy into electrical energy to realize self-powering of intelligent electronic devices, thus reducing the burden of battery replacement and charging, and improving the usage time and efficiency of electronic devices. Through finite element simulation, this study successfully designed high-performance thermoelectric generator and made it into wearable thermoelectric module by adopting “rigid device - flexible connection” method. It was found that higher convective heat transfer coefficient on cold-end leads to larger effective temperature difference and better power generation performance of device in typical wearable scenario. Meanwhile, at same convective heat transfer coefficient on the cold-end, longer TE leg length leads to larger temperature difference established at both ends of device, larger device output power and open-circuit voltage. However, when the convective heat transfer coefficient increases to a certain level, optimization effect of increasing TE leg length on device power generation performance will gradually diminish. For devices with fixed temperature difference between two ends, longer TE leg length leads to higher resistance of TEG, resulting in lower device output power but slight increase in open-circuit voltage. Finally, sixteen 16×4×2 mm2 TEGs (L=1.38 mm, W=0.6 mm) and two modules were fabricated and tested. At hot end temperature Th=33 ℃ and cold end temperature Tc=30 ℃, the actual maximum output power Pout of TEG is about 0.2 mW, and the actual maximum output power Pout of TEG module is about 1.602 mW, which is highly consistent with the simulated value. This work brings great convenience to research and development of wearable thermoelectric modules and provides new, environmentally friendly and efficient power solution for wearable devices.